tbuckley/cabot-search huggingface dataset:
Abstract 12887: Lightning Strikes Twice - A Case of Light Chain and Attr Amyloidosis
Authors: Sruti Prathivadhi-Bhayankaram, Shareef Mansour
Journal: Circulation (2022)

The most common subsets of amyloidosis that affect the heart include light chain (AL) and transthyretin (ATTR). While both types cause diffuse amyloid fibril deposition within the interstitial space of the myocardium, they arise from two different precursors. AL amyloidosis results from misfolded monoclonal light chains, whereas ATTR amyloidosis results from misfolded transthyretin monomers. This distinction is essential as it suggests that a diagnosis of one disease does not exclude the existence of the other. We present a unique case of a patient with evidence of both systemic ATTR and AL amyloidosis occurring concurrently. An 80-year-old male with a past medical history of severe mitral regurgitation S/p mechanical mitral valve replacement, rotator cuff tear, bilateral carpal tunnel syndrome, and multiple hospitalizations for decompensated systolic heart failure was referred to cardiomyopathy clinic. He presented with class III New York Heart Association (NYHA) symptoms, including significant limitations in activity due to dyspnea. An echocardiogram demonstrated severe left ventricular hypertrophy with a low global longitudinal strain, an apical sparing pattern suspicious of amyloidosis. Monoclonal gammopathy workup showed an elevated lambda free light chain. Subsequent bone marrow biopsy demonstrated plasma cell dyscrasia and amyloid deposition in hypocellular bone marrow. Mass spectrometry showed both lambda light chain and transthyretin amyloid protein. He had elevated cardiac biomarkers, speaking for advanced cardiac involvement, together with nephrotic range proteinuria. He was started on chemotherapy/immunotherapy, with daratumumab, bortezomib and dexamethasone. He was in end stage heart failure requiring inotropic support. Few weeks after chemotherapy, he transitioned toward hospice care. In conclusion, we present a rare case of ATTR and AL amyloidosis coinciding simultaneously that demonstrates the importance of having high index of suspicion for this disease, a stepwise and thorough diagnostic approach highlighting the importance of mass spectroscopy after amyloid protein detection.
Abstract 13752: Coronary Artery Bypass Grafting Demonstrates Lower Mortality Rates Compared to Percutaneous Coronary Intervention for Multivessel Coronary Artery Disease: An Updated Systematic Review and Meta-Analysis
Authors: Muhammed K Elfaituri, Ala Khaled, AHMED TAREK SAEED BENGHATNSH, Ahmed Msherghi, Ahmed Elfaituri, Elham Omran, Hazem Abdelkarem Faraj
Journal: Circulation (2022)

Introduction: Treating individuals with stable multivessel coronary artery disease (CAD) and retained ventricular function is still debatable. Percutaneous coronary intervention (PCI) and coronary bypass grafting (CABG) are all options for treatment, and they are all employed in tandem with rigorous secondary prevention. One technique's significant long-term mortality benefit over the other is still debatable for multivessel disease management. Hypothesis: To compare the long-term mortality and complications of coronary artery bypass graft (CABG) versus Percutaneous Coronary Intervention (PCI) among patients with multivessel disease. Methods: Pubmed/Medline, EMBASE, Cochrane, Web of Science, Scopus, and grey literature were searched in March 2022. We only included randomized clinical trials (RCTs) that reported the outcome differences between CABG and PCI. The primary outcome was long-term all-cause mortality. The secondary outcomes were re-intervention rate and major adverse cardiac events (MACE). The statistical analysis was performed using Comprehensive Meta-analysis software version 3. Results: A total of 6 Randomized Control Trails (RCTs) studies were included in the analysis comprising 7,126 patients (3558 PCI and 3568 CABG). The median follow up period was 6.33 years. Long-term mortality from any cause (after 2 years follow up or more) was significantly higher in PCI group compared to CABG group (HR: 1.44; 95% CI, 1.25-1.67; P &lt; 0.01; I 2 = 18.78%). This trend was consistent among diabetic patients (HR: 1.39; 95% CI, 1.14-1.69; P &lt; 0.01; I 2 = 23.73%). CABG procedure was associated with lower rate of additional or repeat intervention (RR: 0.25; 95% CI, 0.17-0.37; P &lt; 0.01; I 2 = 74.4%). Cardiovascular-specific mortality and MACE were lower among CABG group compared to PCI (RR: 0.77; 95% CI, 0.58-0.95; P &lt; 0.01; I 2 = 0%), (RR: 0.77; 95% CI, 0.64-0.93; P &lt; 0.01; I 2 = 0%), respectively. Conclusions: The study shows that CABG provides lower long-term mortality rates, including diabetic patients, a lower rate of repeat intervention, and lower major adverse cardiac events. Therefore, CABG is an effective and safe approach for patients with multivessel diseases compared to PCI, especially in the long term.
Abstract 13329: Intralipid Protects the Heart in Late Pregnancy Against Ischemia/Reperfusion Injury via Inducing Mir122 by Targeting Pkm2
Authors: Laila Aryan, Lejla Medzikovic, Min Li, Gregoire Ruffenach, Shadie Rahman, Ehsan Bastanhagh, Leana Esdin, Wasila Sun, Mansoureh Eghbali
Journal: Circulation (2022)

INTRODUCTION: We have shown hearts of late-pregnant (LP) rats have higher vulnerability to ischemia-reperfusion injury (IRI) compared to non-pregnant (NP) rats, and administration of intralipid (ITLD), a clinically safe fat emulsion, at the onset of reperfusion protects the LP rat heart against IRI. Our goal is to decipher the mechanisms for the ITLD-mediated cardioprotection in LP against IRI. Methods: We occluded the left anterior descending coronary artery of female Sprague-Dawley rats (2-3 months old NP and LP, 20-21 days pregnant) for 45 minutes followed by 3 hours reperfusion. The ITLD group was given ITLD at the onset of reperfusion (5mg/kg of 20%). We assessed myocardial necrosis via TTC staining and sent the hearts for microRNA-microarray profiling (Ocean Ridge Biosciences). In vitro, female cardiomyocytes were transfected either miR122 mimic, miR122 inhibitor, or scramble control (40uM), followed by 3 hours hypoxia and 6 hours reoxygenation. We collected human blood samples from NP, LP, and LP coronary heart disease (CHD) patients. P&lt;0.05 was considered statistically significant. Values are expressed as mean±SEM. Results: MicroRNA-microarray profiling showed microRNA-122-5p (miR122) is downregulated 4-fold in the heart of LP rats subjected to IRI compared to healthy pregnant rats and upregulated 10-fold in the heart of LP rats that received ITLD at reperfusion, which we confirmed with qPCR (0.32±0.12, 90.2±10.3, n=5 animals/group). miR122 is significantly decreased in the plasma of healthy LP women compared to healthy NP women (0.6±0.16, LP n=9, NP n=7) and decreased in LP women with CHD compared to healthy LP (0.43±0.13, CHD n=5). TargetScan showed PKM2 to be a target of miR122. We confirmed significantly increased PKM2 in LP IRI rat myocardium compared to NP IRI (1.88±0.32) and significantly decreased in LP IRI rat administered ITLD (0.32±0.18). MiR122 overexpression in female cardiomyocytes subjected to hypoxia/reoxygenation (H/R) significantly decreased PKM2 (0.35±0.12), apoptosis (0.77±0.12) and oxidative stress (0.51±0.12), while miR122 knockdown expressed the opposite effect (n=4). Conclusions: Intralipid protects the heart in late pregnancy against ischemia/reperfusion injury by upregulating miR122, which targets PKM2.
Abstract 13640: Sex Differences in Heart Failure With Reduced Ejection Fraction in the GALACTIC-HF Trial
Authors: Maria A Pabon porras, Jonathan Cunningham, Brian Claggett, Rafael Diaz, Gary Michael Felker, John J McMurray, Marco Metra, Stephen Heitner, Stuart Kupfer, Fady Malik, Scott Solomon, John R Teerlink
Journal: Circulation (2022)

Introduction: Women with heart failure with reduced ejection fraction (HFrEF) are undertreated with guideline recommended therapy and experience worse quality of life compared with men. Low enrollment of women in HFrEF outcomes trials has limited inferences about drug efficacy in women. We investigated sex-differences in baseline characteristics, clinical outcomes, and response to omecamtiv mecarbil in the GALACTIC-HF trial. Methods: The GALACTIC-HF trial randomized patients with symptomatic HFrEF with EF of 35% or less to omecamtiv mecarbil or placebo. Baseline characteristics for male and female participants were compared using parametric or non-parametric tests. Risk of the primary endpoint, heart failure event or cardiovascular death, was compared between sexes using Kaplan-Meier curves and Cox regression adjusted for 13 relevant clinical covariates. Treatment effect heterogeneity was evaluated by the sex*treatment interaction term. Results: Of the 8,232 patients enrolled, 1749 (21.2%) were women. Women had lower total Kansas City Cardiomyopathy score (59.1 vs 65.8, P&lt;0.001) and were less likely to be treated with ARNI (17.5% vs 20.0%, P=0.02), SGLT2 inhibitor (1.5% vs 2.9% P=0.001), ICD (24.5% vs 33.7%, P&lt;0.001) or CRT (11.5% vs 14.7%, P&lt;0.001). Compared to men, women had lower rates of the primary end point (hazard ratio [HR] 0.89 95% CI 0.81-0.97, p=0.01), which persisted after covariate adjustment (HR 0.85 [95% CI 0.77-0.92], p=0.001). Sex did not significantly modify treatment effect of omecamtiv mecarbil on the primary endpoint (p-interaction = 0.37). Women had higher rates of any reported adverse event but lower risk of serious adverse event leading to treatment discontinuation. Conclusions: Women with HFrEF had worse quality of life, were less likely to be treated with guideline-based therapies and had 15% lower risk of HF event or cardiovascular death compared with men. The effect of omecamtiv mecarbil did not significantly differ by sex.
Abstract 13193: Prevalence of Late Gadolinium Enhancement Following Pediatric Heart Transplantation Increases With Time Since Transplantation
Authors: Andrew A Lawson, Kae Watanabe, Lindsay Griffin, Christina Laternser, Michael Markl, Cynthia K Rigsby, Melanie Sojka, Joshua D Robinson, Nazia Husain
Journal: Circulation (2022)

Introduction: Chronic graft failure in pediatric heart transplant recipients (PHT) is associated with myocardial fibrosis on explanted specimens. Cardiac magnetic resonance imaging (CMR) is a validated, non-invasive method to detect myocardial fibrosis via the presence of late-gadolinium enhancement (LGE). In adult heart transplant recipients, LGE is associated with increased risk of hospitalization and death. We describe LGE on CMR among PHT and its associations with clinical and graft characteristics. Methods: We performed a retrospective chart review of all PHT who underwent CMR over a 6-year period at a single center (81 CMR studies, 59 unique patients). Two independent reviewers assessed the presence and distribution of LGE using the AHA 17-segment model. Clinical history and CMR-derived volumetry/ejection fraction were obtained; differences between LGE+ and LGE- PHT were evaluated. Results: Mean age at CMR was 14.8±4.6y; mean time since transplant was 7.3±5.0y. CMR indication was routine surveillance (without active rejection or history of cardiac allograft vasculopathy) in 63% (51/81) of studies. LGE was present in 36% (29/81). LGE patterns included: posterior hinge-point 27% (22/81), lateral wall 15% (12/81), and extensive, involving &gt;4 AHA segments, 7% (6/81) (Figure). Reviewing initial CMR per PHT (n=59), LGE+ patients were older (17 vs. 13y; p=0.001), with greater time since transplant (8.3 vs. 5.7y; p= 0.041). They demonstrated increased indexed LV end-systolic volume (35 vs. 29 ml/m2; p=0.011) and decreased LV ejection fraction (56.2 vs 60.6%; p=0.015). There were no significant differences in history of moderate/severe rejection or cardiac allograft vasculopathy. Conclusions: LV LGE was seen in about a third of PHT patients, more commonly in older patients with longer time since transplantation. Grafts with LGE show remodeling with lower LV ejection fraction. CMR-derived LGE may improve surveillance of chronic graft failure in PHT.
Abstract 13089: Noninvasive Panoramic Mapping of Rotations and Rate With Adenosine Challenge Predicts Ablative Outcomes in Persistent Atrial Fibrillation Patients
Authors: David Calvo, Lucia Salinas, Pablo Martinez-Camblor, Rut Alvarez, Amaia Martinez, Miguel Soroa, Daniel García-Iglesias, Omer Berenfeld
Journal: Circulation (2022)

Introduction: Ablation outcomes in persistent atrial fibrillation (AF) are suboptimal. Hypothesis: Characterizing the adenosine effects in non-invasive panoramic mapping can guide ablation to increase long-term freedom of arrhythmias. Methods: Persistent AF patients (N=25, mean±SD: 15.3±8.4 mo) underwent non-invasive panoramic mapping (CardioInsight, Medtronic) twice at baseline (B1 and B2) and then during 12 mg adenosine (Ado) peak effect. Reproducible rotational domains (≥2 rotations) were thereafter ablated (3.2±1.3 sites/patient). Data were exported to determine dominant frequencies (DFs) using short FFT technique with 0.1 Hz resolution and correlation with simultaneous intracardiac recordings (p&lt;0.001). Results: Areas with stable DFs at B1 and B2 (
Abstract 13147: Formate Stimulates S-Nitrosylation and Mitochondrial Activity to Induce Cardioprotection
Authors: Raihan Kabir, Haley Garbus, Obialunanma V Ebenebe, Nicole Taube, Deepthi Ashok, Brian O'Rourke, Mark J Kohr
Journal: Circulation (2022)

Formate (FM) is a substrate in one-carbon metabolism, and recent studies implicate its function in both health and disease, but a role in the heart remains unexplored. Research from our group demonstrates that the loss of formaldehyde dehydrogenase, which oxidizes formaldehyde into FM, ameliorates sex-dependent cardioprotection against ischemia-reperfusion (I/R) injury in the female mouse heart. Considering that FM depletion may be detrimental, we tested the hypothesis that FM yields cardioprotective benefit in a model of I/R injury. Hearts from male and female mice (n=5-10/group) were subjected to ex vivo I/R injury with or without FM via Langendorff perfusion. FM significantly enhanced post-ischemic functional recovery in male hearts (27.1%, 95% CI 10.8 to 45.9, p=0.0023; females: 9.5%, 95% CI -6.9 to 27.8, p=0.2020) and decreased infarct size (males: -24.6%, 95% CI -35.1 to -12.2, p&lt;0.0001; females: -3.7%, 95% CI -9.6 to -0.3, p=0.1128), indicating that FM protects the myocardium against I/R injury. Although FM had a greater protective effect in male hearts than in female hearts, plasma FM levels were greater in female mice, suggesting that FM-mediated cardioprotection may already exist near steady state in females. Mechanistically, cardiomyoblasts stimulated with FM exhibited a significant increase in total protein S-nitrosylation (SNO) without changing nitric oxide synthase (NOS) phosphorylation or protein expression; this was suppressed by NOS inhibition, suggesting that FM contributes to NOS-dependent NO cycling in the heart. FM-treated cardiomyocytes and cardiomyoblasts also exhibited significant increases in mitochondrial marker protein expression, metabolic activity, and maximal oxygen consumption, demonstrating an enhanced respiratory capacity to respond to increased energetic demand. Furthermore, FM treatment significantly increased phospho-activation of the energy regulator AMPKα and the protein expression of PGC-1α targets, indicating a potential upregulation in mitochondrial biogenesis. Taken together, these data suggest that FM may stimulate protein SNO and mitochondrial activity to protect the heart against I/R injury.
Abstract 14040: Mechanical Aortic Strain Promotes Expression of Proteolytic Matrix Markers in Abdominal Aortic Aneurysm
Authors: Raj Patel, Mario Figueroa, Victoria Mattia, Ying xiong, Rupak Mukherjee, Jeffrey A Jones, Jean M Ruddy
Journal: Circulation (2022)

Introduction: Serum biomarkers for abdominal aortic aneurysms (AAA) have been identified, but the prognostic relevance has remained unclear. Mechanical activation of aortic VSMCs can elicit production of interleukin-6 (IL-6), a cytokine consistently elevated in AAA. Expecting that stressed native aortic cells may drive degenerative remodeling, we hypothesize that biomarkers focused on matrix proteolysis may be elaborated directly from the aortic wall and assessed as an indicator of aortic strain. Methods: AAA was induced in C57Bl/6 mice with peri-adventitial CaCl 2 (n=5). Terminal procedure at 21 days quantified aortic diameter (AoD) by digital microscopy, obtained blood sampling, and collected aortic tissue. Aortic ultrasound (Vevo3100 with VevoVasc Software) was conducted on Days 0 and 21 to assess AoD and aortic strain parameters. Tissue and serum were analyzed to quantify IL-6 and the proteolytic matrix markers: matrix metalloproteinase-9 (MMP-9), Cathepsin S (CtsS), Cystatin C (CysC), and osteoprotegerin (OPG). Aortic VSMCs underwent mechanical stimulation with 12% Stretch and subsequent QPCR for expression of proteolytic matrix markers (n=4). Groups were analyzed by T-test and ANOVA. Results: At 21 days, all mice in AAA group developed true aneurysms by digital microscopy (&gt;50% dilation compared to internal baseline), and this correlated to measurements from transabdominal ultrasound. Aortic strain assessment indicated increased stiffness parameters in AAA (elevated Pulse Wave Velocity, decreased Distensibility, and decreased Global Radial Strain). The AAA group also had significantly elevated levels of IL-6, MMP-9, and OPG (p&lt;0.05 versus Control for each), with a trend toward increased CtsS and CysC. Alternatively, Stretch VSMCs demonstrated upregulated expression of IL-6, CysC, and OPG (p&lt;0.05 vs Static), while the proteases MMP-9 and CtsS remained unchanged. Conclusion: Mechanical activation of aortic VSMCs can stimulate expression of biomarker proteins associated with AAA, but protease production may rely on the inflammatory infiltrate to promote degenerative matrix remodeling. Further investigation into the source of common AAA biomarkers will provide insight for effective integration into patient care.
Abstract 13949: Age-Dependent Detection of Atrial Fibrillation With Implantable Cardiac Monitors in Patients With Cryptogenic Stroke
Authors: Tobias Uhe, Janina Keilitz, Jörg Berrouschot, Rolf Wachter
Journal: Circulation (2022)

Introduction: Prolonged and intensified rhythm monitoring is recommended to detect atrial fibrillation (AF) in patients with cryptogenic stroke (CS). Continuous monitoring using implantable cardiac monitors (ICM) results in AF detection rates of up to 30%. Although higher age has been identified as an independent risk factor for AF after CS, there are no specific recommendations for the implantation of ICM in younger patients. Hypothesis: AF dectection in young patients (&lt; 60 years) with CS and continuous rhythm monitoring is low. Methods: From 02/2014 to 11/2021, 186 patients (mean age 65 ± 12 years) with cryptogenic stroke were included in this analysis. All patients underwent 72-h ECG monitoring, transcranial Doppler Ultrasound and transthoracic echocardiography according to current guidelines. Follow-up was performed by means of a regular outpatient presentation every three months and included medical history, physical examination, and interrogation of the ICM. AF was defined as any episode of absolute arrhythmia &gt;30 seconds. Results: AF was detected in 62 patients (33 %) during a mean follow-up of 36 ± 23 months. AF was found in 6 % (3/52), 27 % (17/62), 56 % (31/55) and 65 % (11/17) (p &lt; 0.001) in patients aged &lt; 60 years, 60-69 years, 70-79 years and ≥ 80 years, respectively (see Figure 1). All patients with AF under 60 years had an impaired systolic left ventricular function (left ventricular ejection fraction &lt; 50 %). Conclusions: In cryptogenic stroke patients, detection of Atrial Fibrillation by implantable cardiac monitors increases with advanced age. In patients younger than 60 years, Atrial Fibrillation was only detected in patients with impaired systolic left ventricular function. The diagnostic benefit of ICM implantation in young patients with cryptogenic stroke and preserved LV function is limited. Possibly positive predictors for AF detection should be identified and considered in the decision to implant cardiac monitors.
Abstract 13176: Overexpression of BANF1 is Linked to Cardiac Pathologies in Progeria Patients
Authors: Selene G Perales, Vinoth Sigamani, Thennavan P Ulaganathan, SHEEJA RAJASINGH, Rajasingh Johnson
Journal: Circulation (2022)

Introduction: Hutchinson-Gilford progeria (HGP) is a genetic disorder caused by a single nucleotide mutation in the Lamin A gene. This mutation causes the production of the abnormal lamin A protein called progerin. Children affected by this disorder age rapidly and die at an early age, mostly from cardiac pathologies. Another similar progeroid syndrome is Nestor-Guillermo progeria, in which the patients exhibit accelerated aging but have a longer life span. This latter syndrome is caused by a mutation that silences the BANF1 gene. Hypothesis: We hypothesize that BANF1 is linked to cardiovascular disease in Hutchinson-Gilford progeria patients. This gene could be targeted to reduce cardiac pathologies and increase the lifespan of patients with HGP. Methods: We obtained skin fibroblasts from two HGP patients and their respective parents from the Progeria Foundation. We successfully reprogrammed the fibroblasts into induced pluripotent stem cells by a safe non-viral method and further differentiated them into induced cardiomyocytes (iCMCs). Then, we performed multiple analyses to compare the iCMCs of the patients, their parents, and control iCMCs. Results: Through in-silico protein analysis, we were able to identify a relationship between nuclear lamina proteins and BANF1, which is also correlated to cardiac-specific proteins GATA4 and NKX2.5 ( Figure A ). Additionally, through qPCR ( Figure B ) and Western Blot ( Figure C ) analyses, we identified a significant difference in BANF1 expression between the progeria patient iCMCs and the other iCMCs. BANF1 was overexpressed in patient iCMCs, whereas, it had normal expression in patient fibroblasts when compared to control cells. Conclusions: We believe that BANF1 could be a good target for future therapeutic approaches to minimize cardiac pathologies in HGP patients and extend their lifespan.